Work in this laboratory has been focused on the determination of three-dimensional structures of larger proteins in solution by NMR, with a particular emphasis on protein-protein, protein-ligand and protein-DNA complexes. A considerable effort has been placed on the development of three- and four-dimensional heteronuclear NMR to extend the application of NMR as a method for determining three-dimensional structures of proteins in solution beyond the limits of conventional two-dimensional NMR (-100 residues) to molecules in the 150- to 400- residue range, and to develop new NMR methods for determining long range order a priori, including the dependence of heteronuclear relexation data on diffusion anisotropy and the use of residual dipolar couplings. Solution structures of a number of proteins have been determined. These include the complexes of the transcription factors GAGA, AreA and HMG-I/Y with DNA, the DNA MuA binding domains of the Mu transposase, the 30 kDa (259 residue) N terminal domain of Enzyme I of the PTS pathway, the 40 kDa complex of the N-terminal domain of enzyme I with the histidine containing protein HPr (40 kDa), the complete 44 kDa trimeric ectodomain of gp41, the N-terminal domain of HIV-1 integrase, and the barrier-to-autointegration factor BAF.